Delirium

Key messages

• Despite its prevalence in palliative care, delirium is underdiagnosed, especially hypoactive delirium. [1-3] Diagnosis is important for management, prognostication, and in order to counsel families. [4,5] The onset of delirium can be associated with a worsening prognosis. [5-7]
• Delirium in palliative care patients can be a potentially reversible condition. [8]
• Delirium is more common in patients with previous cognitive impairment or dementia. [9]
• Delirium causes significant distress to patients, families and staff [10] and makes it challenging to assess and treat other problems such as pain or depression. [5]
• Symptom fluctuation means assessment should be part of routine care and is most accurately assessed if it is monitored regularly rather than intermittently.
• There are many validated tools which can be used including the commonly used Confusion Assessment Method (CAM) [11,12]
• There is often more than one predisposing and precipitating factor for delirium in palliative care. [8]
• There is limited evidence to support the use of, barbiturates or phenothiazines in the treatment of delirium in palliative care. [8]
• Reducing factors that contribute to delirium, such as room/environment/care setting changes or day/night disruption and minimising the medication burden wherever possible, with special attention to psychoactive drugs can reduce the incidence of delirium. [8]
• Educating and counselling caregivers is an important aspect of managing patients at risk for delirium, or when delirium is diagnosed.

Evidence summary

Definition and prevalence

Delirium is defined as a condition of disturbed consciousness, with reduced ability to focus, sustain or shift attention. The DSM 5 [13]- revised diagnostic criteria for delirium require:

• disturbance of consciousness with a reduced ability to focus, sustain, or shift attention
• altered cognition or a perceptual disturbance (which is not better accounted for by dementia),
• symptoms develop over hours to days and tend to fluctuate during the course of the day, and
• evidence of an aetiological cause for the delirium.

Delirium may be

• hyperactive (presenting with agitation, hyperarousal, and restlessness), or
• hypoactive (presenting with drowsiness, lethargy and reduced levels of arousal), or
• a mixed pattern in which the symptoms fluctuate between hyperactive and hypoactive. [14]

Delirium is extremely common in palliative care patients, with estimates that over 40 percent of patients will experience delirium and the prevalence increasing to over 80 per cent at the end of life. [15-17] Toward the end of life delirium, when combined with agitation may also be referred to as terminal restlessness. Delirium is an independent predictor of mortality. [5,6,15,18]

Assessment

Delirium is underdiagnosed, due in part, to the difficulty in assessing it. [3,15] It remains challenging to diagnose, particularly in children [19] and older people. [20] Hypoactive delirium in particular is under-diagnosed and is the most frequent subtype of delirium in palliative care settings. [1] In a recent systematic review an issue identified with screening or diagnostic tools for delirium were the level of training required to use them and the length of time it takes to administer them. [21] Some of the more commonly used screening tools are the Confusion Assessment Method (CAM), which requires specific training for optimal use, the Delirium Rating Scale, which appears to work best in older patients, and the Memorial Delirium Assessment Scale, may be best used to measure delirium severity. [12,22] Another review also recommended the Observational Scale of Level of Arousal (OSLO) and the Richmond Agitation and Sedation Scale (RASS) as easy to use and appropriate for use in older people. [21] Assessment of delirium is difficult in children and there is low level evidence to support assessment tools for this group. [19]

Terminal restlessness is a cluster of symptoms and perhaps is a poorly understood and overly used term in the palliative care community. Most often described are a combination of agitation and altered mental state, occurring close to the end of life and may be referred to as agitated delirium. [8] There is no agreed definition of this condition. Its relationship with delirium, and its management and potential for reversibility are poorly understood. Assessment must include a consideration of alternative diagnoses. The differential diagnosis for this symptom complex may include: delirium, poorly controlled physical symptoms such as pain, itch, urinary retention or faecal impaction in a patient who is obtunded; akathisia, myoclonus and other movement disorders; partial complex seizures; paraneoplastic limbic encephalitis; and PTSD or other psychotic disorder.

Treatment

Delirium may be reversible, although there is evidence that in some patients it can be persistent [23] and associated with longer term cognitive problems. [24] Much of the evidence about prognosis and treatment of delirium comes from the aged care and critical care literature. However, the focus of care in these populations may be different from that in palliative care, particularly in very advanced disease. [5] In palliative care patients, delirium is frequently multifactorial, and when the main precipitant is irreversible, or due to other factors (for example patient wishes, risk or burden of the interventions) the decision may be made not to pursue active investigation.

Factors which should be considered as possible contributors to delirium in a palliative care patient, and treated as appropriate, include:

• Infection
• Metabolic and biochemical disorders (e.g. renal failure, hypercalcaemia, hyponatraemia, dehydration, hypoxia, hypercapnia)
• Hepatic encephalopathy
• Structural cerebral disease (e.g. primary or secondary cancer, leptomeningeal disease, radiotherapy to the brain)
• Medications (e.g. psychoactive medications such as benzodiazepines, opioids, corticosteroids, antidepressants, or medications with an anticholinergic effect)
• Drug withdrawal (e.g. alcohol, benzodiazepines, nicotine)
• Environmental (hospital admission and associated procedures, uncorrected sensory deficits e.g. vision and hearing).

When delirium is determined as a cause of distress in a dying patient, sedation may be the appropriate goal of treatment, and antipsychotics and benzodiazepines are currently the mainstay of therapy. [8] See pharmacological management. Non pharmacological approaches to delirium in the last days of life can always be implemented.

Delirium can have a distressing effect on family and carers. The high levels of stress experienced by the family of patients with delirium may be exacerbated by the potential irreversibility of the condition and the concern that the patient may die before the delirium abates. [18] Providing carers with information about the causes and potential course of delirium can be useful and reduce distress. [18] Caregivers also found information about how to act around people with delirium useful. [18]

Treatment of delirium is addressed in greater detail in sub-sections on:

• Pharmacological Management
• Non-pharmacological Management
  

Practice implications

• Delirium is underdiagnosed, despite its prevalence in palliative care. [1,8] The symptoms of delirium can mask the presence of other conditions, such as pain.
• Assessment for symptoms of delirium should be part of routine care. It is most accurately assessed if it is monitored regularly rather than being screened for intermittently. There are a number of validated tools which can be used including the Confusion Assessment Method (CAM) [15,21,25]
• Pharmacological management of delirium is at present based on expert opinion and, on that basis, low dose haloperidol can be recommended as first line treatment. [16]
• There is evidence for the impact of environmental factors on cognitively vulnerable patients. [20] It is important to consider clinical practices and features of the palliative care environment which may increase the risk or severity of delirium, or worsen disorientation, and to minimise these (e.g. room and staff changes, day / night disruption, avoidable immobilisation and catheterisation, making sure patients have their hearing aids and glasses, and so on).
• Educating and counselling caregivers is an important aspect of managing patients at risk for delirium, or when delirium is diagnosed. [18,26]

Evidence gap

• It is unclear whether hyperactive and hypoactive delirium have the same pathophysiology, prognostic significance and responses to treatment. [14] The pathophysiology, assessment and management of terminal restlessness has not been well studied.
• Multicomponent intervention studies modify the environment to prevent or reduce the duration of delirium. [20] Whether this approach is likely to be effective in palliative care settings has not yet been studied. However it is likely that the hospitalised elderly population in which it has shown benefit has similarities with many patients in the palliative setting.
• Placebo-controlled trials are still needed to answer the question of whether and which antipsychotics are effective in the treatment of delirium, which targeted symptoms they impact on, whether they improve delirium resolution, and how they should be titrated. [17]
• Education programs to improve the identification and management of delirium are being trialled with some positive outcomes. [26]
• Trials of the impact of melatonin on delirium in intensive care patients are underway and may provide a new direction for research in palliative care. [27]